A Safety and Efficacy Study of FCR001 Cell Therapy in Previously Transplanted Living Donor Kidney Recipients

A Single-arm, Multi-center, Exploratory Safety and Efficacy Study of FCR001 Cell-based Therapy to Induce Donor-specific Tolerance in Previously Transplanted Recipients of a Kidney From a Living Donor, and Safety in FCR001 Donors

An open-label study to assess the safety, tolerability, and efficacy of FCR001 cell therapy in adult recipients 3-12 months after kidney transplantation from a living donor.

The purpose of this study is to assess the safety, tolerability, preliminary efficacy, and overall benefit of FCR001 cell therapy in previously transplanted recipients of a kidney from a living donor.

FCR001 is a novel, cryopreserved allogeneic somatic cell therapy, derived from mobilized peripheral blood mononuclear cells from the same donor as the allograft, and containing hematopoietic progenitor cells, facilitating cells, and αβ T cells. The rationale is to establish durable chimerism and donor-specific tolerance in the recipient enabling freedom from chronic immunosuppression (IS) and its associated toxicities.

Main Inclusion Criteria:

1. Recipient age ≥18 years old.
2. Donor age ≥18 and ≤60 years old at the time of signing informed consent.
3. Recipient of a first kidney transplant from a living donor 3-12 months prior to signing informed consent.
4. Stable renal allograft function ≥60 mL/min/1.73m^2 prior to screening (defined as <25% decrease in eGFR (by Modification of Diet in Renal Disease formula [MDRD4]) between the last 2 consecutive visits and per investigator judgment).
5. Donor between 3 weeks and 12 months after kidney donation, willing to undergo mobilization, apheresis, and 12-month safety follow-up.

Main Exclusion Criteria (Recipient and Donor):

1. Donor/recipient crossmatch positive at time of living donor kidney transplantation.

2. Recipient or donor with use of other investigational drugs within 30 days (or within 5 drug half-lives) of signing informed consent.

3. Recipient or donor with history of hypersensitivity to any of the study drugs or drugs of similar chemical classes.

4. Recipient and donor who are identical twins.

5. Pregnant or nursing (lactating) woman.

6. Recipient or donor with history of malignancy or premalignant syndrome (e.g., myelodysplastic syndrome, monoclonal gammopathy of renal significance [MGRS], monoclonal gammopathy of unknown significant [MGUS]) of any organ system (other than localized excised non-melanomatous lesions of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

7. Recipient or donor with known bone marrow aplasia.

   Main Exclusion Criteria (Recipient-Only):

8. Multi-organ or cell transplant recipient.

9. Blood type ABO incompatible with donor.

10. Positive donor-specific antibody (DSA) at any time pre- or post-transplant (to be confirmed within 30 days prior to FCR001 infusion).

11. Panel Reactive Antibodies (PRA) >80% at the time of living donor kidney transplantation.

12. Induction with alemtuzumab at the time of living donor kidney transplantation.

13. History of acute rejection (biopsy-proven or suspected and treated) or recurrent kidney disease following living donor kidney transplantation.

14. Findings consistent with acute rejection or recurrent disease on the Screening biopsy.

15. Demonstrated intolerance to maintenance immunosuppression with tacrolimus and MMF or MPS.

16. Being maintained on oral corticosteroids (prednisone >10 mg/day or equivalent).

17. Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV). Recipients with history of HCV infection may participate if there is a documented history of treatment with an anti-HCV agent and either one (1) documented negative PCR at least three (3) months after last dose of treatment, or two (2) documented negative PCRs at least 2 weeks apart over a maximum of 4 weeks.

18. Positive for BKV, CMV, or EBV by PCR at screening.

19. Having any baseline condition requiring or anticipated to require chronic or intermittent use of systemic steroids or other IS (e.g., autoimmune disease, asthma) throughout the course of the study.

20. Having a body mass index (BMI) < 18 or > 35 kg/m^2.

21. Requiring systemic anticoagulation, (e.g., for hypercoagulation disorders, deep vein thrombosis, atrial fibrillation) that cannot be temporarily interrupted with would preclude renal biopsy.

22. Having contraindication to TBI according to local radiologist.

23. History of autologous or allogeneic hematopoietic progenitor or mesenchymal stem cell transplant prior to signing informed consent.

    Main Exclusion Criteria (Donor-Only):

24. Biologically unrelated (i.e., no genetic relationship) female donor transplant to male recipient.